Dimethylformamide → 5-(tert-Butoxy)picolinonitrile

Participants

Reaction Steps

To NaOtBu (1.57 g, 16.4 mmol) in HMPA (6 mL) was added DMF (6 mL), followed by 5-fluoropyridine-2-carbonitrile (1 g, 8.19 mmol) and the reaction mixture was stirred for 16 hours under an atmosphere of nitrogen. The reaction mixture was diluted with water (100 mL) and extracted with DCM (3×50 mL) and layers were separated. The organics were washed sequentially with water (50 mL) and sat. aq. NaHCO3 solution (50 mL) and the organic layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-50% EtOAc/hexanes to give 5-tert-butoxypyridine-2-carbonitrile (0.90 g, 62%) as a yellow solid. ESI-MS m/z calc. 176.0. found 177.5 (M+1)+; Retention time: 1.3 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J=2.7, 0.5 Hz, 1H), 7.67-7.56 (m, 1H), 7.41-7.31 (m, 1H), 1.52-1.38 (m, 10H). To 5-tert-butoxypyridine-2-carbonitrile (0.75 g, 4.26 mmol) in ethanol (10 mL) was added NaOH (4.3 mL of 5 M, 21.3 mmol) and the reaction mixture was heated at 85° C. for 1 hour. The reaction mixture was cooled, concentrated in vacuo and diluted with ethyl acetate (50 mL). The organic layer was washed with mixture of brine solution (10 mL) and 6N HCl (3 mL). The organic layer was separated, dried over MgSO4 and concentrated in vacuo to give 5-tert-butoxypyridine-2-carboxylic acid (0.82 g, 99%) as a yellow solid. ESI-MS m/z calc. 195.1. found 196.1 (M+1)+; Retention time: 0.62 minutes (3 min run).

Provenance & Evidence